Evaluation of BACE1 Silencing in Cellular Models. (21st June 2009)

• Record Type: Journal Article
• Authors: Sierant, Malgorzata; Kubiak, Katarzyna; Kazmierczak-Baranska, Julia; Warashina, Masaki; Kuwabara, Tomoko; Nawrot, Barbara
• Other Names: Austen Brian Academic Editor.
• Is Part Of: International journal of alzheimer's disease. Volume 2009(2009)
• Publication Date: 2009-06-21
• Subjects: Alzheimer's disease -- Periodicals; 616.831005
• DOI: 10.4061/2009/257403
• Languages: English
• ISSNs: 2090-8024

Abstract

Abstract : Beta-secretase (BACE1) is the major enzyme participating in generation of toxic amyloid-beta (Aβ ) peptides, identified in amyloid plaques of Alzheimer's disease (AD) brains. Its downregulation results in decreasing secretion of Aβ . Thus, BACE1 silencing by RNAi represents possible strategy for antiamyloid therapy in the treatment of AD. In this study, a series of newly designed sequences of synthetic and vector-encoded siRNAs (pSilencer, pcPURhU6, and lentivirus) were tested against overexpressed and endogenous BACE1 in several cell lines and in adult neural progenitor cells, derived from rat hippocampus. SiRNAs active in human, mouse, and rat cell models were shown to diminish the level of BACE1. In HCN A94 cells, two BACE1-specific siRNAs did not alter the expression of genes of BACE2 and several selected genes involved in neurogenesis (Synapsin I, β III-Tubulin, Calbidin, NeuroD1, GluR2, CREB, MeCP2, PKR), however, remarkable lowering of SCG10 mRNA, coding protein of stathmin family, important in the development of nervous system, was observed.